Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Six children with clinical and hematologic features of juvenile chronic myelogenous leukemia (JCML) underwent bone marrow transplantation (BMT) using T cell-depleted marrow from non-HLA-matched related or closely HLA-matched unrelated donors. Patient ages ranged from 1.2 to 5 years. Four patients received cytoreductive chemotherapy prior to BMT conditioning, and four had undergone pretransplant splenectomies. The donor-recipient matching included: four transplants disparate at one HLA locus (three from unrelated donors and one from a related donor), one transplant disparate at two HLA loci, and one transplant from a one haplotype-mismatched donor. All patients were MLC reactive with their donors. Graft-versus-host disease (GVHD) prophylaxis consisted of in vitro T cell depletion with a monoclonal antibody directed against CD3, and complement in conjunction with cyclosporin A begun on day -1. Conditioning included busulfan, cytosine arabinoside, cyclophosphamide, methyl-prednisolone, and hyperfractionated total body irradiation. All patients engrafted, with median time to neutrophils greater than 500 x 10(6)/l and platelets greater than 25 x 10(9)/l of 20 and 21 days, respectively. Acute GVHD was less than or equal to grade II in all patients. Two patients died of infection (Candida, CMV) at days 74, 157. One patient relapsed at day 177, and subsequently died on day 939. Three patients are alive and disease free at 180 +, 1610 + and 2400 + days from BMT. Although intensive chemotherapy may play a role in providing transient disease control in patients with JCML, allogeneic BMT is the only curative therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Allogeneic marrow transplantation using T cell depletion for patients with juvenile chronic myelogenous leukemia without HLA-identical siblings. 157 10

Two patients treated by unrelated bone marrow transplantation were reported. Case 1 was an eight-year-old boy with Morquio's disease received bone marrow graft from an HLA one-locus mismatched, MLC non reactive unrelated donor. The patient was prepared with conventional dose of cyclophosphamide, and thoracoabdominal irradiation. For the prophylaxis of GVHD, three drug regimen consisted of methotrexate (MTX), cyclosporine A (CsA), and prednisolone (PSL) was administered. Engraftment was prompt, and grade I of acute GVHD developed, which resolved with increased dose of PSL. Case 2 was a ten-month-old boy with juvenile chronic myelogenous leukemia received bone marrow graft from an HLA fully matched, MLC non reactive unrelated donor. Preconditioning regimen consisted of total body irradiation, VP-16, and cytosine arabinoside. MTX, CsA, and methylprednisolone were administered to prevent GVHD, but grade II of acute GVHD developed, which resolved with prolonged course of PSL. Both cases are alive and well, without chronic GVHD. In conclusion, unrelated donor bone marrow transplantation may be a useful to treat hematologic malignancies, aplastic anemia, and some inherited diseases.
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PMID:[Result of allogeneic bone marrow transplantation from unrelated donor]. 239 12

BMT is a well-established treatment for children with ALL in second remission, ANLL in first and second remission and children with JCML and CML. Improvements in transplantation technology and supportive care have resulted in significant increases in the percentage of long-term survivors of allogeneic marrow transplantation. Newer strategies, such as partially matched donor, unrelated matched donor, and autologous transplants, are bineg pursued to overcome the histocompatability barrier. The development of more effective antileukemic cytoreductive chemotherapy and radiation therapy regimens and better methods of preventing GVHD are areas in which further improvements are necessary. Newer methods of marrow purging, such as the use of monoclonal antibodies linked to immunotoxins, already are being tested. In addition, the recent development of molecularly cloned hematopoietic growth factors, such as CSFGM, may make it possible to improve marrow recovery and hasten return of normal immunologic function, thereby increasing the overall safety of the transplant procedure. It is hoped that these innovations eventually will increase the overall applicability of BMT and its role in the treatment of leukemia.
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PMID:Bone marrow transplantation for treatment of leukemia in children. 304 59

Allogeneic bone marrow transplantation is the treatment of choice for many childhood leukemias. The donor of choice-an HLA matched sibling-is only available about 30% of the time. Unrelated donors are an alternative choice. In this report, we describe the results of unrelated donor bone marrow transplants (BMT) in 50 children with leukemia (25 acute lymphoblastic leukemia [ALL], 3 acute myeloid leukemia [AML], 3 juvenile chronic myelogenous leukemia [JCML], 10 chronic myeloid leukemia [CML]) or myelodysplastic syndrome (MDS; 9). The median age of the 31 male and 19 female patients was 9 years (range 2 to 18). Only 13 patients were serologically matched at HLA-A, B, DR, and DQ with their donors; 6 of these were reactive in mixed lymphocyte culture. The other 37 patients were mismatched for one (36 patients) or more (1 patient) HLA antigens. Pretransplant conditioning included cytosine arabinoside, cyclophosphamide, fractionated total body irradiation (TBI) (with lung, liver, and more recently, kidney shielding), and methylprednisolone. High-risk patients also received busulfan. Graft-versus-host disease (GVHD) prophylaxis consisted of T-cell depletion with IgM monoclonal antibody T10B9 plus complement and posttransplant cyclosporine-A. Forty-nine patients (98%) engrafted. Median times to greater than 500 polymorphonuclear leukocytes (PMN)/microL and greater than 25,000 platelets/microL were 18 and 20 days, respectively. Acute GVHD > or = grade II occurred in 16 patients (33%); 13 (81%) of these died. Chronic GVHD developed in 30 of 40 patients at risk, but was extensive in only 5. Event-free survival (EFS) for all patients was 44% +/- 7% (median follow-up was 49 months), and overall survival was 50 +/- 7%. Patients with low-risk disease (ALL or AML in first or second remission and CML in chronic phase) had a better EFS than children with high-risk disease (60% v 34%, P = .07). There was no significant difference in EFS between patients who were serologically matched with their donors (46%) and those who were partially mismatched (43%) (P = .97). These data compare favorably with published reports for children transplanted with HLA-matched sibling donors and should encourage earlier consideration of unrelated donor BMT in children with leukemia or myelodysplasia.
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PMID:Unrelated bone marrow donor transplants for children with leukemia or myelodysplasia. 772 69

Four consecutive children with myelodysplastic syndromes (MDS) underwent matched allogeneic bone marrow transplantation (BMT). Ages ranged from 3.2 to 6.3 years. Diagnosis was assessed according to FAB classification: refractory anemia-RA (n = 1), RA with excess of blasts (RAEB) (n = 1), and juvenile chronic myelogenous leukemia (JCML) (n = 2). Initial treatment included transfusions for all of them, splenectomy (n = 2) and chemotherapy (n = 1). Patients were all prepared with busulfan 21 mg/kg (480 mg/m2), cytosine arabinoside 24,000 mg/m2, melphalan 140 mg/m2. Graft-versus-host disease (GVHD) prophylaxis associated cyclosporine-methotrexate. Engraftment was prompt and complete in all children. Toxicity included severe mucositis (n = 3), moderate veno-occlusive disease (n = 2), acute GVHD (n = 3), chronic GVHD (n = 1). Sequelae have not yet been seen. All patients are alive and disease-free with a follow-up ranging from 7 to 35 months, with a Karnofsky score of 90-100%. Combined busulphan conditioning can offer an alternative to total body irradiation-based regimens in order to avoid late side-effects in children.
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PMID:Intensified conditioning regimen with busulfan followed by allogeneic BMT in children with myelodysplastic syndromes. 792 Mar 11

Ten children with myelodysplastic syndrome underwent an allogeneic bone marrow transplantation (BMT) with an intensified conditioning regimen. The median age of the patients was 8 years (range 2-10), and included 6 males and 4 females. The subtype of the disease was refractory anemia (RA) in 4, RA with excess blasts (RAEB) in 4, RAEB in transformation (RAEB-T) in 1, and juvenile chronic myelogenous leukemia (JCML) in 1. All patients were conditioned with high-dose cytosine arabinoside (12000 mg/m2), cyclophosphamide (120 mg/kg) and either total body irradiation (10-13.2 Gy) or busulfan (16 mg/kg or 560 mg/m2). Cyclosporine A and/or methotrexate were used for the prophylaxis of graft-versus-host disease (GVHD). Engraftment was prompt in all but one patient. Severe acute GVHD (grade 3) (n = 1), interstitial pneumonitis (n = 1) and veno-occlusive disease of the liver (n = 1) occurred. The disease relapsed in one patient with RAEB-T. Seven of the 10 patients were alive and disease free 2-74 months after BMT. The disease-free survival rate at 4 years was 69 +/- 15%. All surviving patients were in the full performance status. The examined children with MDS tolerated this intensified conditioning regimen well.
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PMID:Therapeutic trial of intensified conditioning regimen with high-dose cytosine arabinoside, cyclophosphamide and either total body irradiation or busulfan followed by allogeneic bone marrow transplantation for myelodysplastic syndrome in children. 911 98

It has been unclear whether a graft-versus-leukemia (GVL) effect assists in the control of juvenile myelomonocytic leukemia (JMML) following allogeneic bone marrow transplant. We describe a patient with JMML who relapsed early after an unrelated donor transplant, and following withdrawal of immunosuppression developed graft-versus-host disease (GVHD). Associated with GVHD the proportion of donor cells measured by variable nucleotide tandem repeat (VNTR) analysis increased, and peripheral blasts and cutaneous disease were eliminated. These findings strongly suggest that GVL has a role in the control of JMML.
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PMID:Graft-versus-leukemia is sufficient to induce remission in juvenile myelomonocytic leukemia. 970 31

The purpose of this study was to evaluate the outcome of children with juvenile myelomonocytic leukemia (JMML) treated with alternative donor bone marrow transplantation (BMT). Twelve consecutive patients with JMML confirmed by in vitro clonogenic assays underwent alternative donor BMT. Ten patients received pretransplant chemotherapy for one to seven cycles (cytosine arabinoside regimens). Eight underwent splenectomy before the transplant. Donors were unrelated for nine patients and partially matched related for three. Conditioning included total body irradiation for all but one patient. Graft-versus-host disease (GVHD) prophylaxis included in vitro partial T-lymphocyte depletion for five patients with cyclosporine arabinoside, and cyclosporine arabinoside and methotrexate for seven. Acute GVHD developed in all patients, and chronic GVHD developed in 7 of 11 evaluable patients. Relapses occurred in two patients, and two died of transplant-related causes. Eight patients remain in remission with a median follow-up of 31 months after the BMT. The event-free survival rate for this series is 64% (95% confidence interval, 27%-85%). The roles of pretransplant chemotherapy and splenectomy for leukemic reduction to prevent relapse, and the use of conditioning regimens with total body irradiation require study in a larger series of patients. GVHD may be beneficial in preventing relapses, which has been the major cause of treatment failure for these patients.
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PMID:Alternative donor bone marrow transplantation for children with juvenile myelomonocytic leukemia. 1059 53

Juvenile myelomonocytic leukaemia (JMML) is a rare paediatric disease and allogeneic stem cell transplantation is the only curative approach. The roles of pretransplant treatment, conditioning regimen and graft-versus-host disease (GVHD) are still unclear. Eleven children with JMML underwent allogeneic BMT in our institution. Donors were matched unrelated (n = 6) matched siblings (n = 4) and one mismatch family donor. Transplant-related mortality (TRM) was 36%. Three patients relapsed after transplantation. Two of three patients with relapse are in continuous remission after donor lymphocyte infusion or second BMT, respectively. To evaluate the role of pretransplant treatment, conditioning regimen and GVHD, we have summarised our series with other published single centre reports and give an overview on a total of 65 patients with JMML who underwent allogeneic BMT. No significant correlation between pretransplant treatment, conditioning regimen and TRM could be observed. Overall relapse rate is high (47%). TBI is associated with a significantly higher relapse rate (P = 0.012). Other conditioning modalities, intensive chemotherapy and splenectomy prior to stem cell transplantation do not seem to have a significant impact on relapse rate. Patients with or without GVHD showed no significant difference in relapse rate (58% vs 45%). In the event of relapse after transplantation withdrawal of immunosuppression, donor lymphocyte infusion or second transplant was successful in 6/11 patients. Graft-versus-leukaemia effect seems to play an essential role in bone marrow transplantation for JMML.
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PMID:Allogeneic bone marrow transplantation for juvenile myelomonocytic leukaemia: a single centre experience and review of the literature. 1098 83

Juvenile myelomonocytic leukemia(JMML) is a rare myeloproliferative disorder of early childhood. It is usually characterized by peripheral monocytosis, increased level of HbF, and hypersensitivity of hematopoietic progenitors to granulocyte-macrophage colony-stimulating factor and hepatosplenomegaly. The pathogenesis of JMML has been associated with deregulated signal transduction and growth factor hypersensitivity. Allogeneic stem cell transplantation is the only curative approach but the roles of pretransplant chemotherapy, conditioning regimen and graft-versus-host disease are still unclear. Graft-versus-leukemia effect may play an essential role because withdrawal of immunosuppressive therapy and donor lymphocyte infusion was successful in the relapsed patients after transplantation.
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PMID:[Diagnosis and treatment of juvenile myelomonocytic leukemia(JMML)]. 1176 46


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